The general goal of this project is to understand the structure, function, and physiology of the glycoprotein hormones--thyrotropin, chorionic gonadotropin, luteinizing hormone and follicle-stimulating hormone--and to elucidate the role of glycoprotein hormone derangements in human disease. Recent progress in this research area includes the following: demonstration and characterization of carboxyterminal peptide fragments of the choriogonadotropin beta-subunit as markers of malignant trophoblastic disease; elucidation of the critical dependence of the domain of the choriogonadotropin molecule that activates adenylate cyclase on e sialic acid residues of its alpha-subunit; development of methods for comparative studies of metabolism and kinetics of glycoprotein turnover in rats; and delineation of the extended clinical utility of ultrasensitive thyrotropin assays in the management of thyroid disease. Future emphasis of the project will be on structure-activity relationships of choriogonadotropin and thyrotropin analogues at the TSH receptor, functional analysis of the two classes of thyrotropin binding sites in thyroid membranes, metabolic disposal and degradation products of glycoproteins with specific evaluation of the role of hepatic galactose-terminated glycoprotein receptors and endogenous desialylation, and the clinical; relevance of hormonal heterogeneity.